Vascular Alterations in the Prediabetic Condition

糖尿病前期的血管改变

• 批准号: 7090848
• 负责人: Cynthia Cheng
• 金额: $ 15.6万
• 依托单位: THOMAS JEFFERSON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-07-01 至 2009-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7090848
• 关键词: albumins; blood chemistry; blood pressure; cardiovascular disorder; clinical research; disease /disorder onset; glucose tolerance test; human subject; hypertension; insulin sensitivity /resistance; limbs; metabolic syndrome; microscopy; patient oriented research; peripheral blood vessel; prediabetic state; urinalysis; vascular resistance; vasodilation

DESCRIPTION (provided by applicant): Cynthia Cheng MD, PhD is an instructor in Family Medicine. She holds a doctoral degree in Pharmacology. Dr. Cheng's career goal is to become an established investigator in cardiovascular disease research; specifically, she is interested in the early phase of vascular injury in diabetes and hypertension. Together with her mentor Dr. Falkner, Dr. Cheng has developed a concept derived from three well established observations: 1) The morbidity and mortality suffered by patients with diabetes are consequences of vascular disease; 2) Patients with high blood pressure (a disorder of the vasculature) have a greater risk for development of type 2 diabetes; and 3) Insulin resistance precedes type 2 diabetes and is common among patients with hypertension. Therefore, patients with high blood pressure and insulin resistance may have underlying vascular disease that precedes and contributes to the expression of diabetes. Accordingly, the overall hypothesis for this project is: Microvascular disease precedes the onset of clinical diabetes. Subjects with both high blood pressure and the prediabetic condition of insulin resistance plus impaired fasting glucose will have alterations in microvascular structure. The Research Specific Aims are to: 1. Develop a cohort of adults that includes a sample with high blood pressure (130-160 mmHg systolic) who also have insulin resistance, and a sample of age/race/sex matched adults with normal blood pressure (<130 mmHg systolic) and insulin sensitivity. 2. Measure small vessel structure in peripheral nail beds using capillaroscopy. 3. Measure vascular function by forearm blood flow and determine forearm vascular resistance at maximal vasodilation. 4. Determine if there are other markers of vessel injury in the cohort by assessing urinary albumin excretion. To conduct this research plan, Dr Cheng will work in Dr. Falkner's laboratory to master the established procedures on metabolic assessment and forearm blood flow, and Dr. Cheng will develop the methodology to examine microvascular structure by intravital capillary microscopy. Data generated in this project will be utilized to construct hypothesis driven research applications to continue Dr. Cheng's investigations in this area of clinical research. Data obtained from investigations of the early phase of vascular injury may reduce cardiovascular disease morbidity by contributing to improved strategies to identify, prevent and reverse the vascular pathology of diabetes and hypertension.

描述（由申请人提供）： Cynthia Cheng 医学博士、哲学博士是家庭医学讲师。她拥有药理学博士学位。程博士的职业目标是成为心血管疾病研究领域的知名研究者；具体来说，她对糖尿病和高血压的血管损伤的早期阶段感兴趣。郑博士与她的导师 Falkner 博士一起，根据三个公认的观察结果提出了一个概念：1）糖尿病患者的发病率和死亡率是血管疾病的后果； 2) 高血压（一种脉管系统疾病）患者患 2 型糖尿病的风险更大； 3) 胰岛素抵抗先于 2 型糖尿病发生，并且在高血压患者中很常见。因此，患有高血压和胰岛素抵抗的患者可能患有先于糖尿病并导致糖尿病发生的潜在血管疾病。因此，该项目的总体假设是：微血管疾病先于临床糖尿病的发病。同时患有高血压和胰岛素抵抗的糖尿病前期状况加上空腹血糖受损的受试者的微血管结构会发生改变。该研究的具体目标是： 1. 建立一个成年人队列，其中包括具有胰岛素抵抗的高血压（收缩压 130-160 mmHg）的样本，以及具有正常血压（收缩压 <130 mmHg）和胰岛素敏感性的年龄/种族/性别匹配的成年人样本。 2. 使用毛细管镜测量周边甲床的小血管结构。 3. 通过前臂血流量测量血管功能并确定最大血管舒张时的前臂血管阻力。 4. 通过评估尿白蛋白排泄来确定队列中是否存在其他血管损伤标志物。为了开展这项研究计划，郑博士将在福克纳博士的实验室工作，掌握代谢评估和前臂血流的既定程序，并且郑博士将开发通过活体毛细血管显微镜检查微血管结构的方法。该项目生成的数据将用于构建假设驱动的研究应用程序，以继续郑博士在该临床研究领域的研究。从血管损伤早期研究中获得的数据可能有助于改进识别、预防和逆转糖尿病和高血压血管病理的策略，从而降低心血管疾病的发病率。